The biochemical genetics of pyruvate kinase in the mouse.

In all mammalian systems examined so far there is more than one pyruvate kinase isozyme (PK.EC2.7.40). The current literature suggests that there are three isozymes. The first, PK-1, is found as the isozyme of hepatocytes, as a minor isozyme of kidney cortex and intestine and possibly erythrocytes. The second isozyme, PK-M1, is thought to be expressed only in striated muscle, heart and brain. The third isozyme of PK is the kidney type PK, termed PK-M2 (or PK-K). PK-M2 is found in all other adult tissues and in most foetal tissues. Although these three forms have distinct kinetic and physiological properties and are not readily interconvertible the precise relationships between them are not fully elucidated. The pyruvate kinase phenotypes in the mouse have been found by screening both inbred strains and wild populations. Five of these phenotypically different strains have been investigated. Four of the variants have altered erythrocyte and/or liver PK levels and the fifth has an electrophoretically altered muscle PK. It has been shown that one of the strains with reduced erythrocyte PK activity is altered in the structural gene for erythrocyte PK and that in all parameters examined the liver PK and the erythrocyte PK co-segregates. It has therefore been concluded that these two isozymes are coded for by the same structural gene. The strain showing an electrophoretically altered muscle PK has been shown to be a variant of a PK structural gene also, but not that coding for erythrocyte/liver PK. Therefore, there is evidence for two distinct structural genes for mouse PK. The two genes are both autosomal but they are not linked. The investigations on two other variant phenotypes indicate that the difference in the PK profile in each case may be due to PK regulatory gene mutations. One of these regulatory genes is a trans-acting, recessive, X-1inked gene. In addition to the analysis of variant phenotypes methods for the purification of mouse PK have been investigated.